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Living Repository of Millions of T and B Cell Receptor Sequences from Patients with COVID-19

53 Pages Posted: 16 Jun 2020 Publication Status: Under Review

See all articles by Christoph Schultheiß

Christoph Schultheiß

Martin Luther University of Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology

Lisa Paschold

Martin Luther University of Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology

Donjete Simnica

Martin Luther University of Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology

Malte Mohme

University Medical Center Hamburg-Eppendorf - Department of Neurosurgery

Edith Willscher

Martin Luther University of Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology

Lisa von Wenserski

Martin Luther University of Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology

Rebekka Scholz

Martin Luther University of Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology

Imke Wieters

University Hospital Frankfurt - Infectious Diseases

Christine Dahlke

University Medical Center Hamburg-Eppendorf - First Department of Medicine

Eva Tolosa

University Medical Center Hamburg-Eppendorf - Department of Immunology

Daniel G. Sedding

Martin Luther University Halle-Wittenberg - Mid-German Heart Center

Sandra Ciesek

Goethe University Frankfurt - Institute for Medical Virology

Marylyn Addo

University Medical Center Hamburg-Eppendorf - First Department of Medicine

Mascha Binder

Martin Luther University of Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology

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Abstract

We profiled adaptive immunity in COVID-19 patients with active infection or after recovery and created a living repository of currently >14 million B and T cell receptor (BCR/TCR) sequences from blood of these patients. The B cell response showed converging IGHV3-driven BCR clusters closely associated with SARS-CoV-2 antibodies. Clonality and skewing of TCR repertoires was associated with interferon type I and III responses, early CD4+/CD8+ activation and counterregulation by BTLA, Tim-3, PD-1, TIGIT and CD73. Tfh, Th17-like and nonconventional (but not classical anti-viral) Th1 polarizations were induced. COVID-19 specific T cell responses were driven by TCR clusters shared between patients with a characteristic trajectory of clonotypes and traceability over the disease course. Our cohort – especially the subset with effective viral clearance – reveals fundamental insight into adaptive immunity to SARS-CoV-2 with the living repository providing a bottleneck resource for the scientific community urgently needed to inform therapeutic concepts and vaccine development.

Conflict of Interest: The authors declare no competing interests.

Ethical Approval: Blood collection was performed under institutional review board approvals number 2020-039 and 11/17.

Keywords: COVID-19, SARS-CoV-2, TCR, BCR, T cell cluster, B cell cluster, cytokine, immune checkpoint, immune repertoire, next-generation sequencing

Suggested Citation

Schultheiß, Christoph and Paschold, Lisa and Simnica, Donjete and Mohme, Malte and Willscher, Edith and von Wenserski, Lisa and Scholz, Rebekka and Wieters, Imke and Dahlke, Christine and Tolosa, Eva and Sedding, Daniel G. and Ciesek, Sandra and Addo, Marylyn and Binder, Mascha, Living Repository of Millions of T and B Cell Receptor Sequences from Patients with COVID-19. Available at SSRN: https://ssrn.com/abstract=3624431 or http://dx.doi.org/10.2139/ssrn.3624431
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Christoph Schultheiß

Martin Luther University of Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology ( email )

Germany

Lisa Paschold

Martin Luther University of Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology ( email )

Germany

Donjete Simnica

Martin Luther University of Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology ( email )

Germany

Malte Mohme

University Medical Center Hamburg-Eppendorf - Department of Neurosurgery ( email )

Martinistrasse 52
Hamburg, D - 20246
Germany

Edith Willscher

Martin Luther University of Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology ( email )

Germany

Lisa Von Wenserski

Martin Luther University of Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology ( email )

Germany

Rebekka Scholz

Martin Luther University of Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology ( email )

Germany

Imke Wieters

University Hospital Frankfurt - Infectious Diseases ( email )

Germany

Christine Dahlke

University Medical Center Hamburg-Eppendorf - First Department of Medicine ( email )

Martinistrasse 52
Hamburg, D - 20246
Germany

Eva Tolosa

University Medical Center Hamburg-Eppendorf - Department of Immunology

Martinistrasse 52
Hamburg, D - 20246
Germany

Daniel G. Sedding

Martin Luther University Halle-Wittenberg - Mid-German Heart Center ( email )

Emil-Abderhalden-Str. 7
Halle an der Saale
06099 Halle (Saale), DE Sachsen-Anhalt 06099
Germany

Sandra Ciesek

Goethe University Frankfurt - Institute for Medical Virology ( email )

Paul-Ehrlich-Str. 40
Frankfurt, 60596
Germany

Marylyn Addo

University Medical Center Hamburg-Eppendorf - First Department of Medicine ( email )

Martinistrasse 52
Hamburg, D - 20246
Germany

Mascha Binder (Contact Author)

Martin Luther University of Halle-Wittenberg - Department of Internal Medicine IV, Oncology/Hematology ( email )

Germany

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